There is currently little information on the mechanisms by which genetic inheritance and the environment influence body fat mass in humans. Indeed, even the relative importance of genetic inheritance and environmental factors in determining body composition in adults remains controversial. These important issues will be addressed in an investigation of 85 adult adoptees with their biological and adoptive parents, and 37 pairs of adult monozygotic twins adopted into separate families during infancy. This study seeks to define the roles of key factors in determining the influences of genetic inheritance and the environment (both transmitted and non-transmitted components) on body fat mass in adults. The relationships between parameters thought to be involved in energy regulation and body fat mass will be determined using structural equation modeling. The goal of the study is to delineate underlying causes of differences in body fat mass. We anticipate identifying, for the first time, separate causes of genetic and environmental fat transmission that interact within an overall framework of energy regulation. Detailed investigations using accurate methods will be conducted to measure key parameters including body composition, nutrient intakes, dietary restraint, physical activity, substrate oxidation, components of energy expenditure, and specific metabolic parameters related to substrate oxidation. These measurements will be conducted in our Clinical Center and while the subjects lead normal lives at home. Two techniques will be used to measure most of the parameters, because this will increase both statistical power and our ability to delineate causes and effects of body fat mass. Body composition will be measured using dual energy x-ray absorptiometry and underwater weighing with compartmental modeling. Dietary intake will be determined using a home food diary and measurements of intake while the subjects are resident in the research center. Indirect calorimetry will be used to measure substrate oxidation and energy expenditure, and maximum aerobic capacity. Caltrac accelerometers previously validated against the doubly labeled water method, and questionnaires will be used to determine total energy expenditure during 7 days while the subjects live at home. Dietary restraint and sensory preferences for nutrient composition will be assessed using taste tests and questionnaires, and insulin sensitivity and circulating levels of free fatty acids will be determined using standard techniques. The results of this study may well lead to improved methods for the prevention and treatment of obesity, and will help target the direction of future research on the mechanisms of energy regulation.